Monocrotaline pyrrole interacts with actin and increases thrombin- mediated permeability in pulmonary artery endothelial cells

Dennis W Wilson, M. W. Lamé, S. K. Dunston, D. W. Taylor, H. J. Segall

Research output: Contribution to journalArticle

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Abstract

One of the earliest morphologic changes evident in the monocrotaline (MCT) model of pulmonary hypertension in rats is microvascular leak. Whether this represents a direct effect of MCT metabolites or is secondary to inflammatory and thrombotic changes remains uncertain. To determine whether MCT directly affects endothelial cell permeability barrier function, we characterized the interaction of the reactive pyrrole intermediate of MCT (MCTP) with endothelial cell actin and characterized its effects on thrombin- mediated signal transduction and monolayer permeability. Bovine pulmonary endothelial cells (BPAEC) treated with MCTP had altered distribution of filamentous actin evident by fluorescence microscopy. Correlative Western blots and autoradiography of actin isolated from BPAEC treated with 14C- MCTP showed comigration of actin and MCTP-derived 14C. MCTP treatment did not alter cellular free Ca2+ concentrations nor did it interfere with thrombin-mediated intracellular Ca2+ signal. Pretreatment with MCTP significantly augmented the thrombin-mediated transudation of Evan's blue albumin in BPAEC monolayers apparently by increasing the size of intercellular gaps. We conclude that MCTP directly interacts with actin to alter its polymerization state but does not significantly affect endothelial cell response to contractile stimulus. Our results suggest that MCTP may affect endothelial cell barrier function through alterations in intracellular junctions.

Original languageEnglish (US)
Pages (from-to)138-144
Number of pages7
JournalToxicology and Applied Pharmacology
Volume152
Issue number1
DOIs
StatePublished - Sep 1998

Fingerprint

Endothelial cells
Thrombin
Pulmonary Artery
Actins
Permeability
Endothelial Cells
Monocrotaline
Lung
Monolayers
Signal transduction
Evans Blue
Pyrroles
1-methyl-4-cyclohexyl-1,2,3,6-tetrahydropyridine
monocrotaline pyrrole
Fluorescence microscopy
Metabolites
Autoradiography
Fluorescence Microscopy
Pulmonary Hypertension
Polymerization

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Monocrotaline pyrrole interacts with actin and increases thrombin- mediated permeability in pulmonary artery endothelial cells. / Wilson, Dennis W; Lamé, M. W.; Dunston, S. K.; Taylor, D. W.; Segall, H. J.

In: Toxicology and Applied Pharmacology, Vol. 152, No. 1, 09.1998, p. 138-144.

Research output: Contribution to journalArticle

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